Our overall objectives are to study the regulation of production of islet hormones in islet cell monolayer cultures, to determine the functional interrelationships among A-, B-, and D-cells of the islet, to investigate B-cell regeneration and replication, to distinguish growth and metabolic characteristics of fibroblast cultures from nondiabetic and diabetic individuals, to examine the regulatory influence of insulin on certain metabolic functions of cultured cells, to study in a tissue culture system metabolic processes that may be abnormal in diabetes. Our current goals are to examine the role of opiates, prostaglandins, gastrointestinal polypeptides, and islet hormones upon islet hormone release from cultured islet cells, to study recovery from alloxan treatment in guinea pigs as a model system for beta cell renewal both in vivo and in vitro, and to utilize the perifused (superfused) islet cell monolayer culture system to answer questions about the hormone secretory dynamics of cultured islet cells. We will examine in diabetic and nondiabetic human fibroblast cultures the effects of hyperglycemia, insulin, growth hormone, and altered oxygen tension upon cell proliferation and collagen and protein synthesis.